Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-6-18
pubmed:abstractText
Macrophage colony-stimulating factor (M-CSF) influences the proliferation and survival of mononuclear phagocytes through the receptor CSF-1R. The adaptor protein DAP12 is critical for the function of mononuclear phagocytes. DAP12-mutant mice and humans have defects in osteoclasts and microglia, as well as brain and bone abnormalities. Here we show DAP12 deficiency impaired the M-CSF-induced proliferation and survival of macrophages in vitro. DAP12-deficient mice had fewer microglia in defined central nervous system areas, and DAP12-deficient progenitors regenerated myeloid cells inefficiently after bone marrow transplantation. Signaling by M-CSF through CSF-1R induced the stabilization and nuclear translocation of beta-catenin, which activated genes involved in the cell cycle. DAP12 was essential for phosphorylation and nuclear accumulation of beta-catenin. Our results provide a mechanistic explanation for the many defects of DAP12-deficient mononuclear phagocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2916
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
734-43
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19503107-Adaptor Proteins, Signal Transducing, pubmed-meshheading:19503107-Animals, pubmed-meshheading:19503107-Brain, pubmed-meshheading:19503107-Calcium-Binding Proteins, pubmed-meshheading:19503107-Cell Adhesion, pubmed-meshheading:19503107-Cell Cycle, pubmed-meshheading:19503107-Cell Proliferation, pubmed-meshheading:19503107-Cell Survival, pubmed-meshheading:19503107-Cells, Cultured, pubmed-meshheading:19503107-Flow Cytometry, pubmed-meshheading:19503107-Focal Adhesion Kinase 2, pubmed-meshheading:19503107-Green Fluorescent Proteins, pubmed-meshheading:19503107-Immunoblotting, pubmed-meshheading:19503107-Immunohistochemistry, pubmed-meshheading:19503107-Macrophage Colony-Stimulating Factor, pubmed-meshheading:19503107-Macrophages, pubmed-meshheading:19503107-Mice, pubmed-meshheading:19503107-Mice, Inbred C57BL, pubmed-meshheading:19503107-Mice, Inbred Strains, pubmed-meshheading:19503107-Mice, Knockout, pubmed-meshheading:19503107-Mice, Transgenic, pubmed-meshheading:19503107-Microfilament Proteins, pubmed-meshheading:19503107-Phosphorylation, pubmed-meshheading:19503107-Signal Transduction, pubmed-meshheading:19503107-beta Catenin
pubmed:year
2009
pubmed:articleTitle
Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin.
pubmed:affiliation
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural